Quinidine

Summary

Quinidine (CHEMBL1294) is an approved small-molecule α-adrenergic antagonist (ATC C01BA01) targeting SLC29A4, KCNT1, and KCNT2; indicated across 15 conditions including atrial fibrillation and myocardial infarction.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: C01BA01 (+2 more)
• Targets: 16 (SLC29A4, KCNT1, KCNT2…)
• Indications: 15 conditions
• Clinical trials: 22
• Chemistry: 324.4 Da · C20H24N2O2

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL1294
Name	Quinidine
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	441074
ChEBI	CHEBI:28593
ATC	C01BA01, C01BA51, C01BA71
Molecular formula	C20H24N2O2
Molecular weight	324.4
InChIKey	LOUPRKONTZGTKE-LHHVKLHASA-N

SMILES: COC1=CC2=C(C=CN=C2C=C1)[C@@H]([C@H]3C[C@@H]4CCN3C[C@@H]4C=C)O

IUPAC name: (S)-[(2R,4S,5R)-5-ethenyl-1-azabicyclo[2.2.2]octan-2-yl]-(6-methoxyquinolin-4-yl)methanol

ChEBI definition: A cinchona alkaloid consisting of cinchonine with the hydrogen at the 6-position of the quinoline ring substituted by methoxy.

Pharmacological roles (ChEBI): α-adrenergic antagonist, antimalarial, anti-arrhythmia drug, sodium channel blocker, muscarinic antagonist, potassium channel blocker, P450 inhibitor, EC 1.14.13.181 (13-deoxydaunorubicin hydroxylase) inhibitor, drug allergen.

Other ChEBI roles (chemical / environmental): EC 3.6.3.44 (xenobiotic-transporting ATPase) inhibitor.

Also known as: (8r,9s)-quinidine, .beta.-quinidine, Conquinine, Kinidin, Pitayine, Quinidine, quinidine, TCMDC-131239, GNF-Pf-5459, SID11111707, SID11111708, SID17389531

Parent form; salt/anhydrous children: CHEMBL1200437, CHEMBL1435413, CHEMBL2068675, CHEMBL2165709, CHEMBL3707183

Patent coverage: 21,053 distinct patent families (71,943 SureChEMBL compound mentions), from 3 matched compound structure(s). Mentions count patents naming the compound (not distinct inventions), so promiscuous / reference molecules inflate the mention figure — families are the dedup metric.

Targets

Targets

Primary targets (GtoPdb curated mechanism): the Cancer dependency column is the DepMap CRISPR fitness signal (% of screened cell lines dependent on the target).

Gene	Target	Action	pAffinity	Cancer dependency	UniProt
SLC29A4	Plasma membrane monoamine transporter	Inhibition	4.6	0.7%	Q7RTT9
KCNT1	KNa1.1	Antagonist		1.2%	Q5JUK3
KCNT2	KNa1.2	Inhibition		0.1%	Q6UVM3
KCNU1	KCa5.1			0.1%	A8MYU2
KCNK5	K2P5.1			0.7%	O95279
KCNK6	K2P6.1			0%	Q9Y257
KCNK10	K2P10.1			0%	P57789
KCNK16	K2P16.1			0%	Q96T55
KCNK18	K2P18.1			0.1%	Q7Z418
KCNA4	Kv1.4		3.7	0.7%	P22459
KCNA5	Kv1.5		5.2	0.2%	P22460
KCNA7	Kv1.7		4.8	0.5%	Q96RP8
KCND2	Kv4.2		4.9	0.3%	Q9NZV8
KCNH1	Kv10.1		5.8	0.2%	O95259
KCNH5	Kv10.2	Pore blocker	3.8	0.3%	Q8NCM2
SCN5A	Nav1.5	Pore blocker	5	0.2%	Q14524
	VRAC

Broader ChEMBL bioactivity targets: 47 (assay-derived). Sample: Tyrosyl-DNA phosphodiesterase 1, A-type voltage-gated potassium channel KCND2, Multidrug and toxin extrusion protein 1, ATP-binding cassette sub-family C member 4, Solute carrier family 22 member 2, Solute carrier organic anion transporter family member 1A1, 5-hydroxytryptamine receptor 2B, Alpha-2A adrenergic receptor, Cholinesterase, Alpha-2C adrenergic receptor.

Bioactivity

ChEMBL activities: 132 potent at pChembl ≥ 5 of 175 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
CYP2D6	8.7	IC50	2	nM	CHEMBL_ACT_13457830
CYP2D6	8.48	IC50	3.3	nM	CHEMBL_ACT_676595
CYP2D6	8.16	IC50	6.9	nM	CHEMBL_ACT_19449142
CYP2D6	8.14	IC50	7.3	nM	CHEMBL_ACT_20666031
CYP2D6	8.1	Potency	7.9	nM	CHEMBL_ACT_5010464
CYP2D6	8.1	AC50	7.94	nM	CHEMBL_ACT_6006448
CYP2D6	8.09	IC50	8.1	nM	CHEMBL_ACT_22781609
CYP2D6	8.05	IC50	9	nM	CHEMBL_ACT_16621062
CYP2D6	8.05	IC50	9	nM	CHEMBL_ACT_17692368
CYP2D6	8.05	IC50	9	nM	CHEMBL_ACT_17718293
CYP2D6	8.05	IC50	9	nM	CHEMBL_ACT_26599193
CYP2D6	8.05	IC50	9	nM	CHEMBL_ACT_26609239
CYP2D6	8.01	Ki	9.8	nM	CHEMBL_ACT_2490677
CYP2D6	8	IC50	10	nM	CHEMBL_ACT_1473730
CYP2D6	8	IC50	10	nM	CHEMBL_ACT_19103161
CYP2D6	8	IC50	10	nM	CHEMBL_ACT_19300500
CYP2D6	8	IC50	10	nM	CHEMBL_ACT_19315071
CYP2D6	8	IC50	10	nM	CHEMBL_ACT_5186928
CYP2D6	8	IC50	10	nM	CHEMBL_ACT_5201926
CYP2D6	7.96	IC50	11	nM	CHEMBL_ACT_2154815
CYP2D6	7.85	IC50	14	nM	CHEMBL_ACT_2224896
CYP2D6	7.85	IC50	14	nM	CHEMBL_ACT_2361512
CYP2D6	7.85	IC50	14	nM	CHEMBL_ACT_6164120
CYP2D6	7.77	IC50	17	nM	CHEMBL_ACT_14710055
CYP2D6	7.77	IC50	17	nM	CHEMBL_ACT_16584280
CYP2D6	7.75	IC50	18	nM	CHEMBL_ACT_15702005
CYP2D6	7.75	IC50	18	nM	CHEMBL_ACT_24513612
CYP2D6	7.71	IC50	19.6	nM	CHEMBL_ACT_2490673
CYP2D6	7.7	IC50	20	nM	CHEMBL_ACT_1699395
CYP2D6	7.7	IC50	20	nM	CHEMBL_ACT_24925868

Target pathways

Aggregated over 16 target gene(s): SLC29A4, KCNT1, KCNT2, KCNU1, KCNK5, KCNK6, KCNK10, KCNK16, KCNK18, KCNA4, KCNA5, KCNA7, KCND2, KCNH1, KCNH5, SCN5A.

Top Reactome pathways

26 total, by targets touching each:

Pathway	Targets	Genes
Neuronal System	10	KCNA4, KCNA5, KCNA7, KCND2, KCNH1, KCNH5, KCNK10, KCNK16, KCNK18, KCNK6
Potassium Channels	10	KCNA4, KCNA5, KCNA7, KCND2, KCNH1, KCNH5, KCNK10, KCNK16, KCNK18, KCNK6
Muscle contraction	8	KCNA5, KCND2, KCNK10, KCNK16, KCNK18, KCNK5, KCNK6, SCN5A
Cardiac conduction	8	KCNA5, KCND2, KCNK10, KCNK16, KCNK18, KCNK5, KCNK6, SCN5A
Voltage gated Potassium channels	6	KCNA4, KCNA5, KCNA7, KCND2, KCNH1, KCNH5
Phase 4 - resting membrane potential	5	KCNK10, KCNK16, KCNK18, KCNK5, KCNK6
Tandem pore domain potassium channels	4	KCNK10, KCNK16, KCNK18, KCNK6
Fertilization	1	KCNU1
Developmental Biology	1	SCN5A
Tandem of pore domain in a weak inwardly rectifying K+ channels (TWIK)	1	KCNK6
TWIK-related spinal cord K+ channel (TRESK)	1	KCNK18
TWIK-related alkaline pH activated K+ channel (TALK)	1	KCNK16
TWIK related potassium channel (TREK)	1	KCNK10
Sperm Motility And Taxes	1	KCNU1
Reproduction	1	KCNU1
L1CAM interactions	1	SCN5A
Transport of small molecules	1	SLC29A4
Axon guidance	1	SCN5A
Transport of vitamins, nucleosides, and related molecules	1	SLC29A4
SLC-mediated transmembrane transport	1	SLC29A4
Interaction between L1 and Ankyrins	1	SCN5A
Phase 3 - rapid repolarisation	1	KCNA5
Phase 0 - rapid depolarisation	1	SCN5A
Phase 1 - inactivation of fast Na+ channels	1	KCND2
Transport of nucleosides and free purine and pyrimidine bases across the plasma membrane	1	SLC29A4
Nervous system development	1	SCN5A

Dominant GO biological processes

GO term	Targets
monoatomic ion transport	15
monoatomic ion transmembrane transport	15
potassium ion transmembrane transport	14
potassium ion transport	14
transmembrane transport	8
potassium ion export across plasma membrane	4
regulation of membrane potential	4
action potential	4
protein homooligomerization	4
monoatomic cation transmembrane transport	2
regulation of resting membrane potential	2
regulation of atrial cardiac muscle cell membrane repolarization	2
atrial cardiac muscle cell action potential	2
regulation of heart rate by cardiac conduction	2
cellular response to calcium ion	2

Indications & clinical

Indications

15 indications (1 at ChEMBL trial phase 4). Phase below is the highest clinical-trial phase recorded for this drug against each disease — not the molecule’s overall approval status (that is in the Summary).

Indication	Trial phase	MONDO	EFO
atrial fibrillation	3	MONDO:0004981	EFO:0000275
myocardial infarction	3	MONDO:0005068	EFO:0000612
ventricular fibrillation	3	MONDO:0000190	EFO:0004287
amyotrophic lateral sclerosis	3	MONDO:0004976	MONDO:0004976
multiple sclerosis	3	MONDO:0005301	MONDO:0005301
major depressive disorder	2	MONDO:0002009	MONDO:0002009
depressive disorder	2	MONDO:0002050	MONDO:0002050
migraine disorder	2	MONDO:0005277	MONDO:0005277
metabolic dysfunction-associated steatohepatitis	1	MONDO:0007027	EFO:1001249
respiratory syncytial virus infectious disease	1	MONDO:0001577	EFO:1001413
constipation disorder	1	MONDO:0002203	HP:0002019
hepatitis B virus infection	1	MONDO:0005344	EFO:0004197
severe acute respiratory syndrome	1	MONDO:0005091	MONDO:0100096

2 further indication records had no mapped disease name (EFO/MeSH-only) or were duplicates, and are omitted.

Clinical trials

Total trials: 22.

Phase distribution

Phase	Trials
PHASE1	14
PHASE2	4
PHASE3	3
PHASE2/PHASE3	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00000464	PHASE3	COMPLETED	Cardiac Arrest in Seattle: Conventional Versus Amiodarone Drug Evaluation (CASCADE)
NCT00000518	PHASE3	COMPLETED	Electrophysiologic Study Versus Electrocardiographic Monitoring (ESVEM)
NCT00000556	PHASE3	COMPLETED	Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM)
NCT00789165	PHASE2/PHASE3	WITHDRAWN	Empiric Quinidine for Asymptomatic Brugada Syndrome
NCT01882829	PHASE2	COMPLETED	Nuedexta in Treatment-Resistant Major Depression
NCT02153502	PHASE2	COMPLETED	Efficacy, Safety, and Tolerability Study of AVP-786 as an Adjunctive Therapy in Patients With Major Depressive Disorder With an Inadequate Response to Antidepressant Treatment
NCT02176018	PHASE2	COMPLETED	Nuedexta for the Prevention and Modification of Disease Progression in Episodic Migraine
NCT05593757	PHASE2	UNKNOWN	Quinidine Versus Verapamil in Short-coupled Idiopathic Ventricular Fibrillation
NCT01460381	PHASE1	COMPLETED	A Study to Evaluate the Effect of Genotype on LY2216684
NCT01533155	PHASE1	COMPLETED	Study in Healthy Volunteers to Investigate the Effects of Quinidine on the Pharmacokinetics of NKTR-118
NCT01712828	PHASE1	COMPLETED	Effect of P-glycoprotein Inhibition on Lenalidomide Pharmacokinetics in Healthy Males
NCT02171624	PHASE1	COMPLETED	Safety and Pharmacokinetics of Quinidine Alone and in Combination With Dabigatran Etexilate
NCT03610945	PHASE1	COMPLETED	Drug-drug Interaction Study Between EDP-305, Fluconazole and Quinidine in Healthy Volunteers
NCT03755778	PHASE1	COMPLETED	Drug-Drug Interaction Study Between EDP-938, Itraconazole, Rifampin, and Quinidine in Healthy Subjects
NCT04783753	PHASE1	COMPLETED	Drug-Drug Interaction Study Between EDP-514, Itraconazole, Carbamazepine, and Quinidine in Healthy Subjects
NCT05444556	PHASE1	COMPLETED	A Study of Imlunestrant (LY3484356) in Female Healthy Participants
NCT05594602	PHASE1	COMPLETED	Drug-Drug Interaction Study Between EDP-235, Itraconazole, Carbamazepine and Quinidine in Healthy Subjects.
NCT06493409	PHASE1	COMPLETED	A Study to Assess the Effect of Voriconazole and Quinidine on the Pharmacokinetics of a Single Dose of Repotrectinib in Healthy Participants
NCT06704763	PHASE1	COMPLETED	A Drug-Drug Interaction Study of Orforglipron (LY3502970) With Quinidine in Healthy Participants
NCT06847464	PHASE1	COMPLETED	A Drug-Drug Interaction Study to Evaluate the Effects of Itraconazole, Carbamazepine, Quinidine and Fluconazole on the Pharmacokinetics and Safety of EDP-323.
NCT06974565	PHASE1	COMPLETED	A Study to Investigate the Pharmacokinetics of AZD2389 in Healthy Participants When Administered Alone and in Combination With Quinidine
NCT06979388	PHASE1	COMPLETED	A Study to Investigate the Effect of Food on Balcinrenone/Dapagliflozin Pharmacokinetics in Fed and Fasted State and Pharmacokinetics of Balcinrenone When Dosed With a P-gp Inhibitor in Healthy Participants.

Clinical evidence (CIViC)

No CIViC predictive evidence (expected for non-precision-medicine drugs).

Pharmacology

Pharmacogenomics

PharmGKB dosing guidelines (1) — CPIC / DPWG genotype-guided dosing for this drug (drug × pharmacogene):

Guideline	Source	Gene(s)	Dosing	Recommendation
Annotation of DPWG Guideline for quinidine and CYP2D6	DPWG	CYP2D6

PharmGKB also curates 2 clinical and 12 variant annotation(s) for this drug (gene-keyed; see PharmGKB).

Related molecules

Related molecules

Molecules sharing ≥1 of this drug’s curated primary targets, merged from two biobtree sources and ranked by shared-target count, then clinical phase: ChEMBL clinical-stage candidates (development phase ≥2) and PubChem drug-class bioactivity (approved / known drugs acting on the target). Deduplicated by drug name; the drug’s own salt forms are excluded. Note: for a drug with few primary targets a shared-target match can reflect off-target / promiscuous binding rather than the same therapeutic mechanism — the phase ordering surfaces bona-fide therapeutics first.

141 molecules share ≥1 primary target. Top 60 by shared-target count:

Molecule	Source	Status	Shared targets
FLECAINIDE	ChEMBL + PubChem	Phase 4 (approved)	KCNA5, KCNA7, SCN5A
Lidocaine	ChEMBL + PubChem	Phase 4 (approved)	KCNA5, KCNK18, SCN5A
Verapamil	ChEMBL + PubChem	Phase 4 (approved)	KCNA7, SCN5A, SLC29A4
VERNAKALANT	ChEMBL	Phase 4 (approved)	KCNA5, KCND2, SCN5A
Amiodarone	ChEMBL + PubChem	Phase 4 (approved)	KCNA7, SCN5A
CARVEDILOL	ChEMBL + PubChem	Phase 4 (approved)	KCNK10, SCN5A
Desipramine	ChEMBL + PubChem	Phase 4 (approved)	SCN5A, SLC29A4
Diltiazem	ChEMBL + PubChem	Phase 4 (approved)	KCNA5, SCN5A
Haloperidol	ChEMBL + PubChem	Phase 4 (approved)	KCNH1, SCN5A
Imipramine	ChEMBL + PubChem	Phase 4 (approved)	KCNH1, SCN5A
BEPRIDIL	ChEMBL	Phase 4 (approved)	KCNT1, SCN5A
NIFEDIPINE	ChEMBL	Phase 4 (approved)	KCNA5, SCN5A
SERTINDOLE	ChEMBL	Phase 4 (approved)	KCNA5, SCN5A
Belzutifan	PubChem	Approved	KCNA5, SCN5A
Dronedarone	ChEMBL + PubChem	Phase 4 (approved)	KCNA5
PALIPERIDONE	ChEMBL + PubChem	Phase 4 (approved)	SCN5A
AMITRIPTYLINE	ChEMBL	Phase 4 (approved)	SCN5A
AMLODIPINE	ChEMBL	Phase 4 (approved)	SCN5A
ASENAPINE	ChEMBL	Phase 4 (approved)	SCN5A
ASTEMIZOLE	ChEMBL	Phase 4 (approved)	SCN5A
BAZEDOXIFENE	ChEMBL	Phase 4 (approved)	SCN5A
BENZONATATE	ChEMBL	Phase 4 (approved)	SCN5A
CANDESARTAN CILEXETIL	ChEMBL	Phase 4 (approved)	SCN5A
CARBAMAZEPINE	ChEMBL	Phase 4 (approved)	SCN5A
CHLORPROMAZINE	ChEMBL	Phase 4 (approved)	SCN5A
CISAPRIDE	ChEMBL	Phase 4 (approved)	SCN5A
CLEMASTINE	ChEMBL	Phase 4 (approved)	SCN5A
CLOZAPINE	ChEMBL	Phase 4 (approved)	SCN5A
DABIGATRAN ETEXILATE	ChEMBL	Phase 4 (approved)	SCN5A
DARIFENACIN	ChEMBL	Phase 4 (approved)	SCN5A
DARUNAVIR	ChEMBL	Phase 4 (approved)	SCN5A
DASATINIB	ChEMBL	Phase 4 (approved)	SCN5A
DEFERASIROX	ChEMBL	Phase 4 (approved)	SCN5A
DIBUCAINE	ChEMBL	Phase 4 (approved)	SCN5A
DIPHENHYDRAMINE	ChEMBL	Phase 4 (approved)	SCN5A
DOMPERIDONE	ChEMBL	Phase 4 (approved)	SCN5A
DROPERIDOL	ChEMBL	Phase 4 (approved)	SCN5A
DULOXETINE	ChEMBL	Phase 4 (approved)	SCN5A
ETIDOCAINE	ChEMBL	Phase 4 (approved)	SCN5A
FEDRATINIB	ChEMBL	Phase 4 (approved)	SCN5A
FELODIPINE	ChEMBL	Phase 4 (approved)	SCN5A
FLUPHENAZINE	ChEMBL	Phase 4 (approved)	SCN5A
FLUVOXAMINE	ChEMBL	Phase 4 (approved)	SCN5A
ISRADIPINE	ChEMBL	Phase 4 (approved)	SCN5A
LAMOTRIGINE	ChEMBL	Phase 4 (approved)	SCN5A
LETERMOVIR	ChEMBL	Phase 4 (approved)	SCN5A
LOPERAMIDE	ChEMBL	Phase 4 (approved)	SCN5A
LOPINAVIR	ChEMBL	Phase 4 (approved)	SCN5A
LURASIDONE	ChEMBL	Phase 4 (approved)	SCN5A
MEXILETINE	ChEMBL	Phase 4 (approved)	SCN5A
MIBEFRADIL	ChEMBL	Phase 4 (approved)	SCN5A
MITOXANTRONE	ChEMBL	Phase 4 (approved)	SCN5A
MOXIFLOXACIN	ChEMBL	Phase 4 (approved)	SCN5A
NEBIVOLOL	ChEMBL	Phase 4 (approved)	SCN5A
NELFINAVIR	ChEMBL	Phase 4 (approved)	SCN5A
NICARDIPINE	ChEMBL	Phase 4 (approved)	SCN5A
NIMODIPINE	ChEMBL	Phase 4 (approved)	SCN5A
NINTEDANIB	ChEMBL	Phase 4 (approved)	SCN5A
NISOLDIPINE	ChEMBL	Phase 4 (approved)	SCN5A
OLICERIDINE	ChEMBL	Phase 4 (approved)	SCN5A